NMR-based Metabolic Profiling Identifies High Risk of MAFLD Patients With Advanced Fibrosis

NCT ID: NCT05734599

Last Updated: 2023-02-21

Basic Information

• Recruitment Status: UNKNOWN
• Total Enrollment: 1194 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-03-01
• Study Completion Date: 2024-05-01

Brief Summary

This study aim to find out metabolic molecules in blood and urine which could identify high risk of advanced fibrosis in MAFLD patients via NMR-based metabolic profiling.

Detailed Description

Metabolic dysfunction-associated fatty liver disease (MAFLD) is currently the most common liver disease in the world, with an incidence of 29.81% in China. Studies have shown that the severity of liver fibrosis is the most important predictor of disease progression in patients with MAFLD, and the more severe the degree of liver fibrosis, the worse the prognosis. Therefore, discovering non-invasive indicators that can predict the risk and identify people at high risk of MAFLD with advanced liver fibrosis is essential for early clinical intervention in order to improve their clinical prognosis. Some non-invasive tests like Vibration-controlled Transient Elastography (VCTE), Fibrosis-4 Index (FIB-4), and NAFLD fibrosis score (NFS) have been used to evaluate the liver fibrosis state in MAFLD patients, but lack of prospect in metabolic molecular level. Nuclear magnetic resonance(NMR)-based metabolomic profiling can identify and quantify significant biological molecules in tissue extracts, body fluids (blood, urine, cerebrospinal fluid, saliva, etc.), and secretions, and has wide applications in the study of cancer and other metabolic diseases. Therefore, this study intends to collect the demographic characteristics and serological indicators of MAFLD patients detected by liver VCTE, and use NMR profiling to perform metabolomic analysis on their peripheral blood and urine samples, in order to discover potential non-invasive biomarkers that can be used to predict and evaluate MAFLD advanced liver fibrosis, and further verify these MAFLD metabolomic indicators that may be associated with advanced liver fibrosis through multi-center clinical studies, in an attempt to provide ideal non-invasive biomarkers for MAFLD progression prediction and clinical intervention monitoring.

Conditions

Metabolic Dysfunction-associated Fatty Liver Disease; Metabolic Disease

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: CROSS_SECTIONAL

Study Groups

MAFLD-control group

Participants accepted health examinations including vibration-controlled transient elastography in Tongji and Union hospitals who are not MAFLD patients and are willing to participate in this study.

NMR-based metabolic profiling

Intervention Type: DEVICE

Clinical parameters and VCTE results of each patient will be collected. Patients will be grouped into two groups according to VCTE, FIB-4 and NFS, and undergo NMR-based metabolic profiling

MAFLD-high hardness group

Participants accepted health examinations including vibration-controlled transient elastography in Tongji and Union hospitals who are defined to have MAFLD and are willing to participate in this study.

The risk of advanced liver fibrosis was estimated based on the LSM value, FIB-4 score, and NAFLD fibrosis score (NFS), and patients were then divided into groups of low and high hardness according to the risk measured, as shown below:

High hardness group:

participants meet one of the following three requirements: LSM≥ 11.4 kPa；9.9<LSM≤11.4 kPa and NFS≥0.676;9.9<LSM≤11.4 kPa and FIB-4≥2.67.

NFS = -1.675 + 0.037 × age (years) + 0.094 × BMI (kg/m2) + 1.13 × Fasting blood glucose abnormalities / diabetes mellitus (with=1, none=0) + 0.99 × AST/ALT ratio - 0.013 × platelets (×109/L) - 0.66 × albumin (g/dl) FIB-4 = （age(years) x AST [U/L]) / ((PLT [109/L]) x (ALT [U/L])^(1/2))

NMR-based metabolic profiling

Intervention Type: DEVICE

Clinical parameters and VCTE results of each patient will be collected. Patients will be grouped into two groups according to VCTE, FIB-4 and NFS, and undergo NMR-based metabolic profiling

MAFLD-low hardness group

Participants accepted health examinations including vibration-controlled transient elastography in Tongji and Union hospitals who are defined to have MAFLD and are willing to participate in this study.

The risk of advanced liver fibrosis was estimated based on the LSM value, FIB-4 score, and NAFLD fibrosis score (NFS), and patients were then divided into groups of low and high hardness according to the risk measured, as shown below:

Low hardness group:

participants who do not meet the requirements of the high hardness group are low hardness group: LSM < 9.9 kPa；9.9<LSM≤11.4 kPa with NFS < 0.676 and FIB-4<2.67.

NFS = -1.675 + 0.037 × age (years) + 0.094 × BMI (kg/m2) + 1.13 × Fasting blood glucose abnormalities / diabetes mellitus (with=1, none=0) + 0.99 × AST/ALT ratio - 0.013 × platelets (×109/L) - 0.66 × albumin (g/dl) FIB-4 = （age(years) x AST [U/L]) / ((PLT [109/L]) x (ALT [U/L])^(1/2))

NMR-based metabolic profiling

Intervention Type: DEVICE

Clinical parameters and VCTE results of each patient will be collected. Patients will be grouped into two groups according to VCTE, FIB-4 and NFS, and undergo NMR-based metabolic profiling

Interventions

NMR-based metabolic profiling

Clinical parameters and VCTE results of each patient will be collected. Patients will be grouped into two groups according to VCTE, FIB-4 and NFS, and undergo NMR-based metabolic profiling

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

• Patients with MAFLD

• Meet the diagnostic criteria in the 2020 Asian Pacific Association for the Study of the Liver (APASL) Clinical Practice Guidelines for the Diagnosis and Management of Metabolism-Related Fatty Liver Disease
• Liver Vibration-controlled Transient Elastography (FibroTouch) with evidence of hepatic steatosis (CAP value≥ 240db/m)
• Age≥ 18 years

Healthy controls:

• Liver Vibration-controlled Transient Elastography (FibroTouch) showed no fatty liver and no liver fibrosis;
• No history of other chronic diseases, no use of appropriate prescription drugs;
• The amount of alcohol consumed was ≤8 g per day for women and ≤16g per day for men.

Exclusion Criteria

• • Chronic viral hepatitis, alcoholic liver disease or excessive alcohol consumption (more than 30 g of alcohol per day for men and 20 g for women), decompensated cirrhosis;

• Chronic liver disease due to other causes (e.g., autoimmune hepatitis, primary biliary cirrhosis, primary sclerosing cholangitis, hereditary hemochromatosis, Wilson disease, alpha-1 antitrypsin deficiency, celiac disease)
• Imaging findings suggest a malignant mass of the liver;
• Patients with other malignant tumors (excluding cured ones);
• Have secondary obesity due to endocrine, genetic, metabolic, and central nervous system diseases. Judge by professional doctors whether it is hypothalamic obesity, pituitary obesity, hypothyroid obesity, obesity caused by Cushing's syndrome and hypogonadal obesity;
• Have received or are currently receiving medical or surgical treatment for weight loss in the past three months or are currently being treated;
• Weight fluctuations of ≥ 5 kg over the past two months;
• Currently pregnant or nursing;
• Severe cardiovascular and cerebrovascular disease or stage III hypertension;
• Hepatitis B, active tuberculosis, AIDS and other infectious diseases;
• Those who are unable to sign the informed consent form (such as mental illness and drug addiction, etc.).

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Huazhong University of Science and Technology

OTHER

Sponsor Role: lead

Responsible Party

Bin Cheng

professor

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Bin Cheng Doctor

Role: PRINCIPAL_INVESTIGATOR

Tongji Hospital

Locations

Tongji hospital, Tongji Medical College, Huazhong University of Science and Technology

Wuhan, Hubei, China

Countries

China

Central Contacts

Bin Cheng, Doctor

Role: CONTACT

bcheng@tjh.tjmu.edu.cn

027-83663334

Other Identifiers

MAFLD-NMR 2022

Identifier Type: -

Identifier Source: org_study_id